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The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.
We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.
At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.
It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.
The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).
We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.
The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.
Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.
A physical oceanographic, geophysical and marine geological survey of Edward VIII Gulf, Kemp Coast, collected data from conductivity–temperature–depth casts, multi-beam bathymetric swath mapping and 3.5 kHz sub-bottom surveying. Modified circumpolar deep water (mCDW) is observed in Edward VIII Gulf, as well as notable bathymetric features including mega-scale glacial lineations and a 1750 m-deep trough. Sedimentological, geochemical, rock-magnetic and micropalaeontological analysis of two kasten cores document regional palaeoclimate and palaeo-oceanographic conditions over the past 8000 years, with a warm period occurring from c. 8 to 4 ka and a shift to cooler conditions beginning at c. 4 ka and persisting until at least 0.9 ka. Sediment packages > 40 m thick within deep troughs in Edward VIII Gulf present potential targets for higher-resolution Holocene and deglacial climate studies. Despite the presence of mCDW on the shelf, inland bed topography consisting of highland terrain suggests the likelihood of relative stability of this sector of the East Antarctic Ice Sheet.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.
The purpose of this update is to provide the most current information about both the Colorado Adoption Project (CAP) and the Longitudinal Twin Study (LTS) and to introduce the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife), a product of their merger and a unique study of lifespan behavioral development and cognitive aging. The primary objective of CATSLife is to assess the unique saliency of early childhood genetic and environmental factors to adult cognitive maintenance and change, as well as proximal influences and innovations that emerge across development. CATSLife is currently assessing up to 1600 individuals on the cusp of middle age, targeting those between 30 and 40 years of age. The ongoing CATSLife data collection is described as well as the longitudinal data available from the earlier CAP and LTS assessments. We illustrate CATSLife via current projects and publications, highlighting the measurement of genetic, biochemical, social, sociodemographic and environmental indices, including geospatial features, and their impact on cognitive maintenance in middle adulthood. CATSLife provides an unparalleled opportunity to assess prospectively the etiologies of cognitive change and test the saliency of early childhood versus proximal influences on the genesis of cognitive decline.
The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent–child associations, with a focus on mental health and cognitive-related traits. Through CoTEDS, we will have a new lens to examine the roles that parents play in influencing child development, as well as the genetic and environmental factors that shape parenting behavior and experiences. Recruitment is ongoing from the sample of approximately 20,000 contactable adult twins who have been enrolled in the Twins Early Development Study (TEDS) since infancy. TEDS twins are invited to register all offspring to CoTEDS at birth, with 554 children registered as of May 2019. By recruiting the second generation of TEDS participants, CoTEDS will include information on adult twins and their offspring from infancy. Parent questionnaire-based data collection is now underway for 1- and 2-year-old CoTEDS infants, with further waves of data collection planned. Current data collection includes the following primary constructs: child mental health, temperament, language and cognitive development; parent mental health and social relationships; parenting behaviors and feelings; and other socioecological factors. Measurement tools have been selected with reference to existing genetically informative cohort studies to ensure overlap in phenotypes measured at corresponding stages of development. This built-in study overlap is intended to enable replication and triangulation of future analyses across samples and research designs. Here, we summarize study protocols and measurement procedures and describe future plans.
Objective: Post-stroke cognitive impairment is common, but mechanisms and risk factors are poorly understood. Frailty may be an important risk factor for cognitive impairment after stroke. We investigated the association between pre-stroke frailty and acute post-stoke cognition. Methods: We studied consecutively admitted acute stroke patients in a single urban teaching hospital during three recruitment waves between May 2016 and December 2017. Cognition was assessed using the Mini-Montreal Cognitive Assessment (min=0; max=12). A Frailty Index was used to generate frailty scores for each patient (min=0; max=100). Clinical and demographic information were collected, including pre-stroke cognition, delirium, and stroke-severity. We conducted univariate and multiple-linear regression analyses with covariates forced in (covariates included were: age, sex, stroke severity, stroke-type, pre-stroke cognitive impairment, delirium, previous stroke/transient ischemic attack) to investigate the association between pre-stroke frailty and post-stroke cognition. Results: Complete data were available for 154 stroke patients. Mean age was 68 years (SD=11; range=32–97); 93 (60%) were male. Median mini-Montreal Cognitive Assessment score was 8 (IQR=4–12). Mean Frailty Index score was 18 (SD=11). Pre-stroke cognitive impairment was apparent in 13/154 (8%) patients. Pre-stroke frailty was significantly associated with lower post-stroke cognition (Standardized-Beta=−0.40; p<0.001) and this association was independent of covariates (Unstandardized-Beta=−0.05; p=0.005). Additional significant variables in the multiple regression model were age (Unstandardized-Beta=−0.05; p=0.002), delirium (Unstandardized-Beta=−2.81; p<0.001), pre-stroke cognitive impairment (Unstandardized-Beta=−2.28; p=0.001), and stroke-severity (Unstandardized-Beta=−0.20; p<0.001). Conclusions: Pre-stroke frailty may be a moderator of post-stroke cognition, independent of other well-established post-stroke cognitive impairment risk factors. (JINS, 2019, 25, 501–506)
We develop a test, based on the Lagrange multiplier [LM] testing principle, for the value of the long memory parameter of a univariate time series that is composed of a fractionally integrated shock around a potentially broken deterministic trend. Our proposed test is constructed from data which are de-trended allowing for a trend break whose (unknown) location is estimated by a standard residual sum of squares estimator applied either to the levels or first differences of the data, depending on the value specified for the long memory parameter under the null hypothesis. We demonstrate that the resulting LM-type statistic has a standard limiting null chi-squared distribution with one degree of freedom, and attains the same asymptotic local power function as an infeasible LM test based on the true shocks. Our proposed test therefore attains the same asymptotic local optimality properties as an oracle LM test in both the trend break and no trend break environments. Moreover, this asymptotic local power function does not alter between the break and no break cases and so there is no loss in asymptotic local power from allowing for a trend break at an unknown point in the sample, even in the case where no break is present. We also report the results from a Monte Carlo study into the finite-sample behaviour of our proposed test.
Introduction: Smoking is one of the most important risk factors for cardiovascular disease (CVD). Electronic cigarettes (e-cigarettes) are becoming increasingly popular. However, little is known regarding their patterns of use in patients with established CVD.
Aims: We aimed to assess the perceptions and patterns of use of e-cigarettes in patients presenting to a vascular clinic.
Methods: We performed a qualitative study to identify perceptions and beliefs about e-cigarettes. Semi-structured interviews of consecutive patients consenting to participate were performed over five-months. Individuals were recruited from a vascular surgery outpatient clinic. Initial interviews were based on a questionnaire. Further structured interviews were conducted with patients currently using e-cigarettes, which were transcribed and analysed to assess perceptions and patterns of use.
Results/Findings: Four overarching themes emerged: attraction to e-cigarettes as a harm reduction/smoking cessation strategy; uncertainty regarding the risks of e-cigarettes; use of various types of smoking cessation strategies; dual use and often complete relapse to tobacco products.
Conclusions: Patients with established CVD view e-cigarettes as a means of smoking cessation; however, many relapse to tobacco products or use both simultaneously. Further research is necessary regarding the role of e-cigarettes in smoking cessation in this high-risk group.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
Recent modelling estimates up to two-thirds of new HIV infections among men who have sex with men occur within partnerships, indicating the importance of dyadic HIV prevention efforts. Although new interventions are available to promote dyadic health-enhancing behaviours, minimal research has examined what factors influence partners’ mutual engagement in these behaviours, a critical component of intervention success. Actor-partner interdependence modelling was used to examine associations between relationship characteristics and several dyadic outcomes theorised as antecedents to health-enhancing behaviours: planning and decision making, communication, and joint effort. Among 270 male-male partnerships, relationship satisfaction was significantly associated with all three outcomes for actors (p = .02, .02, .06 respectively). Latino men reported poorer planning and decision making (actor p = .032) and communication (partner p = .044). Alcohol use was significantly and negatively associated with all outcomes except actors’ planning and decision making (actors: p = .11, .038, .004 respectively; partners: p = .03, .056, .02 respectively). Having a sexual agreement was significantly associated with actors’ planning and decision making (p = .007) and communication (p = .008). Focusing on interactions between partners produces a more comprehensive understanding of male couples’ ability to engage in health-enhancing behaviours. This knowledge further identifies new and important foci for the tailoring of dyadic HIV prevention and care interventions.
Giant ragweed has been increasing as a major weed of row crops in the last
30 yr, but quantitative data regarding its pattern and mechanisms of spread
in crop fields are lacking. To address this gap, we conducted a Web-based
survey of certified crop advisors in the U.S. Corn Belt and Ontario, Canada.
Participants were asked questions regarding giant ragweed and crop
production practices for the county of their choice. Responses were mapped
and correlation analyses were conducted among the responses to determine
factors associated with giant ragweed populations. Respondents rated giant
ragweed as the most or one of the most difficult weeds to manage in 45% of
421 U.S. counties responding, and 57% of responding counties reported giant
ragweed populations with herbicide resistance to acetolactate synthase
inhibitors, glyphosate, or both herbicides. Results suggest that giant
ragweed is increasing in crop fields outward from the east-central U.S. Corn
Belt in most directions. Crop production practices associated with giant
ragweed populations included minimum tillage, continuous soybean, and
multiple-application herbicide programs; ecological factors included giant
ragweed presence in noncrop edge habitats, early and prolonged emergence,
and presence of the seed-burying common earthworm in crop fields. Managing
giant ragweed in noncrop areas could reduce giant ragweed migration from
noncrop habitats into crop fields and slow its spread. Where giant ragweed
is already established in crop fields, including a more diverse combination
of crop species, tillage practices, and herbicide sites of action will be
critical to reduce populations, disrupt emergence patterns, and select
against herbicide-resistant giant ragweed genotypes. Incorporation of a
cereal grain into the crop rotation may help suppress early giant ragweed
emergence and provide chemical or mechanical control options for
late-emerging giant ragweed.
A microchannel plate was used as an ion sensitive detector in a commercial helium ion microscope (HIM) for dark-field transmission imaging of nanomaterials, i.e. scanning transmission ion microscopy (STIM). In contrast to previous transmission HIM approaches that used secondary electron conversion holders, our new approach detects forward-scattered helium ions on a dedicated annular shaped ion sensitive detector. Minimum collection angles between 125 mrad and 325 mrad were obtained by varying the distance of the sample from the microchannel plate detector during imaging. Monte Carlo simulations were used to predict detector angular ranges at which dark-field images with atomic number contrast could be obtained. We demonstrate atomic number contrast imaging via scanning transmission ion imaging of silica-coated gold nanoparticles and magnetite nanoparticles. Although the resolution of STIM is known to be degraded by beam broadening in the substrate, we imaged magnetite nanoparticles with high contrast on a relatively thick silicon nitride substrate. We expect this new approach to annular dark-field STIM will open avenues for more quantitative ion imaging techniques and advance fundamental understanding of underlying ion scattering mechanisms leading to image formation.
Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk.
The Bovine Respiratory Disease Coordinated Agricultural Project (BRD CAP) is a 5-year project funded by the United States Department of Agriculture (USDA), with an overriding objective to use the tools of modern genomics to identify cattle that are less susceptible to BRD. To do this, two large genome wide association studies (GWAS) were conducted using a case:control design on preweaned Holstein dairy heifers and beef feedlot cattle. A health scoring system was used to identify BRD cases and controls. Heritability estimates for BRD susceptibility ranged from 19 to 21% in dairy calves to 29.2% in beef cattle when using numerical scores as a semi-quantitative definition of BRD. A GWAS analysis conducted on the dairy calf data showed that single nucleotide polymorphism (SNP) effects explained 20% of the variation in BRD incidence and 17–20% of the variation in clinical signs. These results represent a preliminary analysis of ongoing work to identify loci associated with BRD. Future work includes validation of the chromosomal regions and SNPs that have been identified as important for BRD susceptibility, fine mapping of chromosomes to identify causal SNPs, and integration of predictive markers for BRD susceptibility into genetic tests and national cattle genetic evaluations.